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Vitamin D₃ signaling and breast cancer: Insights from transgenic mouse models

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dc.contributor.authorSheng, L.
dc.contributor.authorCallen, D.
dc.contributor.authorTurner, A.
dc.date.issued2018
dc.description.abstractThe biologically active form of vitamin D3 (1,25(OH)2D) regulates epithelial cell differentiation, proliferation, and apoptosis, lending weight to clinical evidence linking vitamin D3 insufficiency to breast cancer incidence and mortality. Local dysregulation of vitamin D3 metabolism has been identified in patients with breast cancer, implying that disruption of 1,25(OH)2D signaling may contribute to breast cancer development in an autocrine or paracrine manner. Mouse mammary glands express the critical enzymes responsible for 1,25(OH)2D synthesis (Cyp2r1 and Cyp27b1), degradation (Cyp24a1), as well as the vitamin D3 receptor (Vdr), and genetically modified mouse models have revealed a great deal about the role of vitamin D3 in cancer initiation and progression. Ablation of Vdr or Cyp27b1 in murine models of mammary cancer reduces the anti-tumor effects of vitamin D3, while elevation of Cyp24a1 levels increases degradation of 1,25(OH)2D, leading to diminished anti-tumor effects. This review discusses the recent transgenic mouse models of vitamin D3 metabolism and the Vdr signaling network, and how these contribute to mammary gland development, and cancer tumorigenesis and progression. Collectively, these mouse models have helped clarify mechanisms of action of vitamin D3 signaling and suggest that activation or restoration of the vitamin D3 regulated pathway is a potential approach for human breast cancer prevention.
dc.identifier.citationJournal of Steroid Biochemistry and Molecular Biology, 2018; 178:348-353
dc.identifier.doi10.1016/j.jsbmb.2018.02.006
dc.identifier.issn0960-0760
dc.identifier.issn1879-1220
dc.identifier.orcidCallen, D. [0000-0002-6189-9991]
dc.identifier.urihttps://hdl.handle.net/11541.2/131188
dc.language.isoen
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.rightsCopyright 2018 Elsevier
dc.source.urihttps://doi.org/10.1016/j.jsbmb.2018.02.006
dc.subjectBreast cancer
dc.subjectCyp24a1
dc.subjectCyp27b1
dc.subjectVitamin D(3)
dc.subjectVitamin D(3) receptor
dc.titleVitamin D₃ signaling and breast cancer: Insights from transgenic mouse models
dc.title.alternativeVitamin D(3) signaling and breast cancer: Insights from transgenic mouse models
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916177210101831

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